Raffick A.R. Bowen

Clinical Associate Professor, Pathology

Bio

Bio

Dr. Raffick Bowen is Clinical Associate Professor of Pathology and the Associate Director of Clinical Chemistry and Immunology Laboratory at Stanford University Medical Center. Dr. Bowen received his license and certification in Medical Laboratory Technology (MLT) from the Canadian Society of Medical Laboratory Technologist and has a license as a Clinical Chemist from the State of California. He completed his BSc in Medical Laboratory Science and PhD focusing on omega-6 and omega-3 fatty acids on brain development with implication to the manufacturing of infant formulas from the University of Alberta. Dr. Bowen completed a post-doctoral diploma in Clinical Chemistry (DClChem) from the University of Toronto and he became a Fellow of the Canadian Academy of Clinical Biochemistry (FCACB). Dr. Bowen has also spent a few years at the National Institutes of Health in Bethesda, Maryland as a Fogarty Post-Doctoral Fellow at the Clinical Center. Dr. Bowen is a Diplomate of the American Board of Clinical Chemistry (DABCC). Also, Dr. Bowen is a Fellow of the American Academy of Clinical Biochemistry (FACB). Dr. Bowen has also completed his Master in Health Administration (MHA) degree from the University of British Columbia.

I believe that philosophy dictates practice and by engaging in this self-reflection process will result in an increased understanding of our beliefs about the nature of our professional work and life.

As a leader, I believe in teamwork, collaboration, and collective decision-making. W. Edwards Deming is the main influence of my management philosophy: It is not enough to do your best; you must know what to do, and then do your best. I also believe that financial accountability, transparency, and continuous improvement are essential for success of a diagnostic laboratory. My vision of Laboratory Medicine is to provide a continuous quality of service that is beyond the expectations of our clients.

Never regard study as a duty, but as the enviable opportunity to learn to know the liberating influence of beauty in the realm of the spirit for your own personal joy and to the profit of the community to which your later work belongs.

Doctor of Philosophy, Unverisity of Alberta, Omega-6 and omega-3 Fatty Acid in Brain Development

Bachelor of Science, University of Alberta, Medical Laboratory Science

Diploma, CSMLS, Medical Technology

Research & Scholarship

Current Research and Scholarly Interests

Blood collection tubes are much more complex devices than is commonly appreciated by clinical laboratorians. Commercial tubes have multiple components that contribute to the optimal formation of serum or plasma for laboratory analysis.

My research has shown that the silicone surfactant, Silwet L-720™, used in blood collection tubes from a major manufacturer interferes with some immunoassays. This surfactant causes desorption of capture antibodies from the solid-phase in some immunoassay reagents. In addition, these tube additives can interfere with other analytical techniques like mass spectrometry.

Since the quality of patient care depends on the quality of all the information that a physician uses in making treatment decisions, blood collection tubes should be manufactured to an extremely high standard like other medical devices. These tube-related interferences unlike patient specimens are not detected by routine quality control or proficiency testing since laboratorians typically do not pour these materials into the tube types used by their lab. Thus, any tube-related interferences will be missed by the clinical lab, which can possibly lead to increased costs due to recollection and retesting, misdiagnosis, erroneous test results, increased turnaround times of test results, delays in patient care, decreased patient satisfaction, and diminished reputation of healthcare institution.

I am currently testing different types of surfactants and tube wall surface modification on immunoassays. This work will hopefully lead to blood collection tubes with minimum or no assay interferences and a better understanding of the effects of blood collection tube surfactant and additives on clinical assays, particularly, immunoassays.

Publications

Journal Articles

Abstract

We demonstrate a simple nonaqueous reaction scheme for transforming the surface of plastics from hydrophobic to hydrophilic. The chemical modification is achieved by base-catalyzed trans-esterification with polyols. It is permanent, does not release contaminants, and causes no optical or mechanical distortion of the plastic. We present contact angle measurements to show successful modification of several types of plastics including poly(ethylene terephthalate) (PET) and polycarbonate (PC). Its applicability to blood analysis is explored using chemically modified PET blood collection tubes and found to be quite satisfactory. We expect this approach will reduce the cost of manufacturing plastic devices with optimized wettability and can be generalized to other types of plastic materials having an electrophilic linkage as its backbone.

Abstract

Several previous studies have described the effects of interfering substances on clinical assay results; however, the effects of exogenous substances, particularly additives from blood collection tubes on quality control (QC) specimens and serum specimens have not been well examined. This study examines the effects of blood-collection tube additives on total triiodothyronine (TT3), and thyroxine (TT4), cortisol, and routine clinical chemistry tests in QC and serum specimens from apparently healthy volunteers.QC and serum specimens were poured or collected into different blood collection tubes. TT3 and TT4, cortisol, and routine chemistry tests were analyzed from the different blood-collection tube types.The findings of this study demonstrate statistically and/or clinically significant blood collection tube-related alterations in the TT3, TT4, and cortisol concentrations of QC specimens and TT4 concentrations from serum specimens.These findings have important implications for clinical laboratories, demonstrating that QC specimens should ideally, like patients' specimens, be poured into blood collection tubes. This strategy would reveal any adverse effects caused by blood collection tubes, which otherwise would not likely be detected by most routine QC practices. The results of this study also show the importance of producing blood collection tubes that contain additives that are truly inert and do not adversely affect clinical laboratory testing.

Abstract

Improper design or use of blood collection devices can adversely affect the accuracy of laboratory test results. Vascular access devices, such as catheters and needles, exert shear forces during blood flow, which creates a predisposition to cell lysis. Components from blood collection tubes, such as stoppers, lubricants, surfactants, and separator gels, can leach into specimens and/or adsorb analytes from a specimen; special tube additives may also alter analyte stability. Because of these interactions with blood specimens, blood collection devices are a potential source of pre-analytical error in laboratory testing. Accurate laboratory testing requires an understanding of the complex interactions between collection devices and blood specimens. Manufacturers, vendors, and clinical laboratorians must consider the pre-analytical challenges in laboratory testing. Although other authors have described the effects of endogenous substances on clinical assay results, the effects/impact of blood collection tube additives and components have not been well systematically described or explained. This review aims to identify and describe blood collection tube additives and their components and the strategies used to minimize their effects on clinical chemistry assays.

Abstract

Total quality in laboratory medicine should be defined as the guarantee that each activity throughout the total testing process is correctly performed, providing valuable medical decision-making and effective patient care. In the past decades, a 10-fold reduction in the analytical error rate has been achieved thanks to improvements in both reliability and standardization of analytical techniques, reagents, and instrumentation. Notable advances in information technology, quality control and quality assurance methods have also assured a valuable contribution for reducing diagnostic errors. Nevertheless, several lines of evidence still suggest that most errors in laboratory diagnostics fall outside the analytical phase, and the pre- and postanalytical steps have been found to be much more vulnerable. This collective paper, which is the logical continuum of the former already published in this journal 2 years ago, provides additional contribution to risk management in the preanalytical phase and is a synopsis of the lectures of the 2nd European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)-Becton Dickinson (BD) European Conference on Preanalytical Phase meeting entitled "Preanalytical quality improvement: in quality we trust" (Zagreb, Croatia, 1-2 March 2013). The leading topics that will be discussed include quality indicators for preanalytical phase, phlebotomy practices for collection of blood gas analysis and pediatric samples, lipemia and blood collection tube interferences, preanalytical requirements of urinalysis, molecular biology hemostasis and platelet testing, as well as indications on best practices for safe blood collection. Auditing of the preanalytical phase by ISO assessors and external quality assessment for preanalytical phase are also discussed.

Abstract

During the development of a testosterone assay by LC-MS/MS, we encountered significant assay interference introduced by blood collection tubes. We examined a number of commonly used blood collection tubes for the presence of interference and its impact on testosterone quantitation.A number of commonly used blood collection tubes were examined by incubation of zero, low and high testosterone concentration samples with them over time, followed by sample preparation using liquid-liquid extraction and analysis by LC-MS/MS. Source of interference was identified by separately incubating blood collection tube coating, stopper and separator gel in clean glass tubes containing zero calibrator.Significant interference was found in some blood collection tubes, with the separator gel identified as the main source. The magnitude of the interference increases over time and mainly affected one of the two testosterone mass transitions used in the quantitation, making it readily detected by the discrepant results obtained by each of the two testosterone mass transitions. We were unable to eliminate the interference by adjustment of the sample preparation procedure, and by changing LC or MS parameters. Accurate quantitation of testosterone is possible when the problematic tubes are avoided, and blood collection tubes free of interference are used instead.Significant LC-MS/MS testosterone assay interference that originated from certain type of blood collection tubes hampered testosterone analysis. Examination of blood collection tube and any other laboratory test tubes for interference should therefore be an integral part of the development and validation of any LC-MS/MS assay used in a clinical diagnostic laboratory.

Abstract

To determine whether tubes containing sodium fluoride negatively bias blood glucose concentration by directly comparing glucose concentrations in paired blood samples collected in tubes containing lithium heparin (Li-Heparin) and tubes containing sodium fluoride/potassium oxalate (NaF-KOx).Paired blood samples from a group of patients (n = 1040) were collected in tubes containing Li-Heparin and tubes containing NaF-KOx at the same time. All Li-Heparin samples were centrifuged soon after collection and were kept cool in transport along with NaF-KOx samples, which were centrifuged at the receiving location after an average transport time of 4 h, but immediately before analysis. Glucose concentrations in the paired samples were determined simultaneously by an automated oxidase method.The mean glucose concentrations for NaF-KOx samples and Li-Heparin samples were 5.7 mmol/l and 6.1 mmol/l, respectively, with a mean difference of 0.39 mmol/l.Rapid separation of heparinised blood is superior to fluoride alone for abrogating glycolytic effects on blood glucose measurements in the clinical laboratory.

Abstract

Besides total triiodothyronine (TT3), total free fatty acids (FFA) concentrations were higher with serum separator tube (SST) than Vacuette tubes.The effects of surfactant, rubber stopper, and separator gel from various tubes were investigated on FFA, beta-hydroxybutyrate (beta-HB), and TT3 with 8 different tube types in blood specimens of apparently healthy volunteers.Compared to Vacuette tubes, serum FFA and TT3 concentrations were significantly higher in SST than glass tubes. Reformulated SST eliminated the increase in TT3 but not FFA. No significant difference was observed for beta-HB concentration among tube types. Surfactant and rubber stoppers from the different tube types significantly increased TT3 but not FFA and beta-HB concentrations. Agitation of whole blood but not serum or plasma specimens with separator gel from SST, reformulated SST and plasma preparation tube (PPT) tubes compared to Vacuette tubes gave higher FFA but not beta-HB levels.Unidentified component(s) from the separator gel in SST, reformulated SST and PPT tubes cause falsely high FFA concentration. In contrast to TT3, falsely high FFA results require exposure of whole blood and not serum to tube constituent(s). The approach employed here may serve as a model for assessing interference(s) from tube constituent(s).

Abstract

A small number of immunoassays on several different types of analyzers were recently adversely affected by tube additives in Becton Dickinson (BD) Vacutainer SST, SST II, and Microtainer blood collection tubes. We examined the effect of a commonly used tube surfactant, Silwet L-720, on immunoassays and the mechanism for the interference.Immunoassays were performed on serum supplemented with Silwet L-720 on the IMMULITE 2500 and AxSYM analyzers. Direct effects of the surfactant on the chemiluminescent detection step of immunoassays and on antibody immobilization on the solid phase were examined.Increasing the final surfactant concentration from 0 to 400 mg/L in serum significantly increased (approximately 51%) the apparent total triiodothyronine (TT3) concentrations measured on the IMMULITE 2500 but not the AxSYM analyzer. Several other competitive, but not noncompetitive, assays were also significantly affected by the surfactant on the IMMULITE 2500 analyzer. The effect was independent of serum components, and the surfactant had no direct effect on chemiluminescence reactions. The capture antibody, however, was displaced from the solid phase by incubation with solutions containing surfactant under conditions similar to the IMMULITE TT3 assay.The Silwet L-720 surfactant, which is used to coat the inner surfaces of tubes, appears to account for previously reported immunoassay interference by BD Vacutainer SST blood collection tubes. One of the mechanisms for the interference is the desorption of antibodies from the solid phase by the surfactant. The results identify an important factor in the selection of suitable blood collection tube surfactants and provide an approach for solving similar tube-assay interference problems in the future.

Abstract

Increased total triiodothyronine (TT(3)) assay results in apparently euthyroid patients triggered an investigation of the effect of blood collection tubes on serum TT(3) and other laboratory assays.We examined potential assay interference for three types of tubes: plastic Greiner Bio-One Vacuette; glass Becton Dickinson (BD) Vacutainer; and plastic BD Vacutainer SST tubes. Serum samples from apparently healthy volunteers (age range, 30-60 years; 15 males and 34 females) were collected in different tube types and analyzed in 17 immunoassays (n = 49), 30 clinical chemistry tests (n = 20), and 33 immunology assays (n = 15). Tube effects were also examined by adding pooled serum to different tube types.TT(3) values, when measured by the IMMULITE 2000 but not the AxSYM analyzer, were significantly higher (P <0.0001) for SST (2.81 nmol/L) than either glass (2.15 nmol/L) or Vacuette (2.24 nmol/L) tubes. The effect was large enough to substantially shift the distribution of patient values, increasing the percentage of values above the reference interval from 11.3% to 35.8%. The degree of interference from SST tubes on TT(3) differed among various tube lots and could be attributed to a tube additive shared by other plastic tubes. Results from several other tests statistically differed among tube types, but differences were not considered to be clinically significant.Assay interferences from blood collection tubes represent challenges to clinical laboratories because they are not detected by the usual quality-control or proficiency testing programs. Laboratories can, however, address this problem by monitoring distribution of patients' results.

Abstract

Both the activated partial thromboplastin time (aPTT) and anti-Xa assay can be used to monitor unfractionated heparin (UFH). Following implementation of an anti-Xa method for heparin dosing protocols in our hospital, we became aware of many patients with discordant aPTT and anti-Xa values.To determine the frequency of discordant aPTT and anti-Xa values in a large cohort of hospitalized patients treated with UFH, as well as the demographics, coagulation status, indication for UFH, and clinical outcomes in this population.All aPTT and anti-Xa values from adults hospitalized between February and August 2009 at Stanford Hospital who were treated with UFH were analyzed. All samples were drawn simultaneously. A polynomial fit correlating aPTT and anti-Xa with a 99% confidence limit was designed. Paired aPTT/anti-Xa values were grouped according to whether the paired values fell within or outside of the concordant area. Patients were placed into groups based on concordance status, and clinical outcomes were assessed.A total of 2321 paired values from 539 patients were studied; 42% of data pairs had a high aPTT value relative to the anti-Xa value. Patients with elevated baseline prothrombin time/international normalized ratio or aPTT frequently demonstrated disproportionate relative prolongation of the aPTT. Patients with at least 2 consecutive high aPTT to anti-Xa values had increased 21-day major bleeding (9% vs 3%; p = 0.0316) and 30-day mortality (14% dead vs 5% dead at 30 days; p = 0.0202) compared with patients with consistently concordant values.aPTT and anti-Xa values are frequently discordant when used to measure UFH in hospitalized patients. A disproportionate prolongation of the aPTT relative to the anti-Xa was the most common discordant pattern in our study. Patients with relatively high aPTT to anti-Xa values appear to be at increased risk of adverse outcomes. Monitoring both aPTT and Xa values may have utility in managing such patients.

Abstract

Identify the etiology of elevated B(12) in autoimmune lymphoproliferative syndrome (ALPS).Peripheral blood of ALPS patients with elevated B(12) and controls were evaluated.Total and holo-haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively. No abnormal B(12)-binding proteins were found. Western blot revealed HC in lymphocyte lysates only from ALPS patients.Elevated concentrations of B(12) found in ALPS patients were due to increased lymphocyte expression of HC.